Neurophysiological biomarkers of treatment response in suicidal ideation: a systematic review

Background: Suicidal ideation (SI) is associated with increased morbidity and is one of the main modifiable risk factors for suicide. While initial evidence indicates the efficacy of several treatments for SI, most treatments were not developed to specifically target SI and are often associated with side effects or high relapse rates. Limited understanding of the neurophysiological basis of SI has hindered the optimization of these treatments. Methods: This systematic review synthesizes the evidence on neurophysiological biomarkers associated with treatment-induced changes in SI in the context of clinical trials. A systematic literature of the Embase, PubMed, and PsycInfo databases was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Results: Twenty-four articles were eligible for inclusion in this review, with most published within the past five years. The studies showed methodological heterogeneity, leading to limited convergence in findings. Many studies were limited by non-randomized study design, concurrent interventions, incomplete treatment protocols, and unvalidated assessments of SI. Despite these limitations, the findings suggest the involvement of the anterior cingulate cortex (ACC) in the anti-suicidal effects of intravenous (IV) ketamine. Notably, this effect was absent in patients treated with oral ketamine, possibly explaining the clinically superior anti-suicidal effects of IV-ketamine compared to the oral administration. Improvements in SI following electroconvulsive therapy and magnetic seizure therapy were associated with activity in the prefrontal cortex (PFC). Conclusion: These findings may indicate that the differential modulation of the ACC and PFC is linked to the acute, yet transient effects of IV-ketamine and the sustained effects of seizure therapies. Future studies designed to prospectively assess the efficacy of SI treatments should include these potential biomarkers of treatment response in their design.